Hello there
It is good to be back after a looong break. With this post I wish to start with another set of questions that have interested me, the ‘how did they know’ kind. I have always been intrigued by the history of a fact, how did the investigator think of investigating it, how did the investigator go about designing the experiment, what were the difficulties they faced, was it easy to get funding for their experiment, and it goes on.
Most of the posts of this type will surprisingly have an answer, which is in contrast to the previous posts. (There is very little original thought involved in writing this, it is mostly letting you all known about what I have read.)
Question for today : How do we know that hepatic stellate cells store vitamin A?
Before we answer this, lets go to the basics.
The liver is a brown colored, kind-of-squishy organ located in the right side of the abdomen, right below the diaphragm. It is responsible for a wide range of functions from synthesis and secretion of important proteins to detoxification of the blood. If you look at the liver with a microscope, you will see interesting patterns based now the animal the liver belongs to. For histology, lets talk humans. The liver consists of 4 major cell types, the hepatocyte, hepatic stellate cells (also called cells of Ito), Kupffer cells and liver sinusoidal endothelial cells. They can be thought of as being organized into small lobules in two ways, portal lobules or hepatic lobules.
Hepatic lobules are organized around the portal vein as hexagons, with each point of the hexagon containing the portal triad (hepatic artery, portal vein and the bile duct).
The portal lobules can be thought of as a triangle with a hepatic vein at each of it’s corner and a portal triad at it’s centre.
You would ask, what is the point of it? And why did anyone think of doing this? Well the answer to that is on the internet (and hopefully another post on this blog)
So, back to hepatic stellate cells.
These cells are present in the space of Disse, which is the space between the hepatic endothelial cells and the hepatocytes. von Kupffer was the first person to describe the hepatic stellate cells, but in a (kind-of) dramatic turn of events, he went on to say that these cells were the same as the phagocytic cells that we know as Kupffer cells today, which lead to confusion, and these stellate cells were sidelined for some time.
The were brought back to the notice of the general scientific audience in the late 1900s. It is here that people started noticing fat filled cells in the space of Disse. It is during this time that people looked at these cells with flouroscence microscope and noted the green chracteristic autoflouroscence of vitamin A. (Now you would say, when and how did we know that vitamin A has a green autoflouroscence? Well dear reading, I donot know, but I hope to turn it into a post someday)
While this is a place to start, it isn’t really a solid proof. Dr Wake and colleagues set out to find out. They took rabbits and gave them supraphysiological doses of Vitamin A and then analyzed their livers, and lo and behold the cells that were hypothesized to be storing vitamin A grew to become plump and chubby. The increase in size was related to the amount of vitamin A given. That sounds like a good enough proof I guess.
BTW, the pictures in the paper by Dr Wake et al are beautiful, do check it out.
A huge thank you to a review by Haruki Senoo and colleagues, which is where I found most of the technical information from.
The introduction though is all from first year med school text book.
Source :
Senoo, H., Yoshikawa, K., Morii, M., Miura, M., Imai, K. and Mezaki, Y. (2010), Hepatic stellate cell (vitamin A-storing cell) and its relative – past, present and future. Cell Biology International, 34: 1247-1272. https://doi.org/10.1042/CBI20100321
Wake K. ‘‘Sternzellen’’ in the liver: perisinusoidal cells with special reference to storage of vitamin A. Am J Anat 1971;132:429–62.
Liver histology image is from Shutterstock
The screen shot from the last paper.
I am not sure if it is alright to keep it on the internet like this. Let me know if it is something that is not allowed.